[show abstract][hide abstract] ABSTRACT: Background. Fatigue in patients with multiple sclerosis (MS) is highly prevalent and severely impacts quality of life. Recent studies suggested that sleep-disordered breathing (SDB) significantly contributes to fatigue in MS. Study Objective. To evaluate the importance of routine respirography in MS patients with severe fatigue and to explore the effects of treatment with continuous positive airway pressure (CPAP). Patients and Methods. We prospectively assessed the presence of severe fatigue, as defined by a score of ≥5.0 on the Fatigue Severity Scale (FSS), in 258 consecutive MS patients. Ninety-seven patients (38%) suffered from severe fatigue, whereof 69 underwent overnight respirography. Results. We diagnosed SDB in 28 patients (41%). Male sex was the only independent associate of SDB severity (P = 0.003). CPAP therapy in 6 patients was associated with a significant reduction of FSS scores (5.8 ± 0.5 versus 4.8 ± 0.6, P = 0.04), but the scores remained pathological (≥4.0) in all patients. Conclusion. Respirography in MS patients with severe fatigue should be considered in daily medical practice, because SDB frequency is high and CPAP therapy reduces fatigue severity. However, future work is needed to understand the real impact of CPAP therapy on quality of life in this patient group.
[show abstract][hide abstract] ABSTRACT: High field magnetic resonance imaging (MRI) provides higher lesion load measurements in patients presenting with clinically isolated syndromes (CIS) suggestive of demyelination and has impact upon the classification of these syndromes and potentially, the diagnosis of multiple sclerosis (MS).
To investigate whether high field MRI can provide an earlier diagnosis of definite MS within the International Panel (IP) and Swanton criteria.
Forty patients presenting with CIS suggestive of MS were included. All patients received multi-sequence MRI at 1.5 Tesla (T) and 3T as well as a neurological assessment at baseline. Follow-up visits including MRI at both field strengths and neurological examinations were scheduled 3-4 and 6-7 months after the first clinical event. Based on MRI and clinical findings, fulfilled IP criteria as well as Swanton criteria were analysed.
At baseline, the higher detection rate of inflammatory lesions using high field MRI leads to higher classifications according to the Swanton criteria in 15 % of the patients. One additional patient was diagnosed with dissemination in space according to Swanton and IP criteria. During follow-up, an earlier diagnosis of definite MS could not be accomplished, neither according to the IP nor to the Swanton criteria.
Although high field MRI shows a higher detection rate of inflammatory brain lesion in CIS and MS patients with an influence according to MRI criteria, this influence does not lead to an earlier diagnosis of lesion dissemination in time and therefore definite MS.
Journal of Neurology 06/2008; 255(8):1159-63. · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to determine the prognostic value of metabolic alterations in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) with special regard to the prediction of conversion to definite MS.
Using a 3T whole-body MR system, a multisequence conventional MRI protocol and single-voxel proton MR spectroscopy (PRESS, repetition time 2000 ms, echo times 38 ms and 140 ms) of the parietal NAWM were performed in 25 patients presenting with CIS at baseline and in 20 controls. Absolute concentrations of N-acetyl-aspartate (tNAA), myo-inositol (Ins), choline (Cho) and creatine (tCr) as well as metabolite ratios were determined. Follow-up including neurological assessment and conventional MRI was performed 3-4 and 6-7 months after the initial event.
Nine patients converted to definite MS during the follow-up period. Compared to controls, those patients who converted to MS also showed significantly lower tNAA concentrations in the NAWM (-13.4%, P = 0.002) whereas nonconverters (-6.5%, P = 0.052) did not. The Ins concentration was 20.2% higher in the converter group and 1.9% higher in the nonconverter group, but these differences did not reach significance. No significant differences could be observed for tCr and Cho in either patient group.
Axonal damage at baseline in patients presenting with CIS was more prominent in those who subsequently converted to definite MS in the short term follow-up, indicating that tNAA might be a sufficient prognostic marker for patients with a higher risk of conversion to early definite MS.
[show abstract][hide abstract] ABSTRACT: To prospectively investigate metabolic changes in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) and to correlate these changes to conventional MR imaging findings in terms of MR imaging criteria.
Multisequence MR imaging of the brain and (1)H-MR spectroscopy of the parietal NAWM were performed in 31 patients presenting with CIS and in 20 controls using a 3. 0 T MR system. MR imaging criteria and International Panel criteria were assessed based on imaging, clinical and paraclinical results. Metabolite ratios and absolute concentrations of N-acetyl-aspartate (tNAA), myoinositol (Ins), choline (Cho), and total creatine (tCr) were determined. The metabolite concentrations were correlated with the fulfilled MR imaging criteria.
In comparison to the control group, the CIS group showed significantly decreased mean tNAA concentrations (-8. 1%, p = 0. 012). Significant changes could not be detected regarding Ins, tCr and Cho. No significant correlations between absolute metabolite concentrations and MR imaging criteria were observed. Patients with and without a lesion dissemination in space showed no significant differences of their metabolite concentrations.
As assessed by (1)H-MRS a significant axonal damage already occurs during the first demyelinating episode in patients with CIS. Conventional MR imaging in terms of diagnostic imaging criteria does not significantly reflect NAWM disease activity in terms of metabolic alterations detected by (1)H-MR spectroscopy.
Journal of Neurology 02/2008; 255(1):56-63. · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: Proton MR spectroscopy ((1)H-MR spectroscopy) is a well-established method for the in vivo investigation of the normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS). Metabolic changes in NAWM are of special interest in patients with clinically isolated syndromes (CIS) suggestive of MS regarding further prognostic classifications. The purpose of this study was to investigate metabolic alterations in NAWM in patients with CIS with use of high-field (1)H-MR spectroscopy and to compare the results to those in patients with an early course of MS.
With use of a 3T whole-body MR imaging system, single-voxel (1)H-MR spectroscopy (PRESS; TR: 2000 ms; TE: 38 ms and 140 ms) of the parietal NAWM was performed in 20 control subjects, 36 patients with CIS, and 12 patients with MS. Metabolite ratios and concentrations of N-acetylaspartate (tNAA), myo-inositol (mIns), choline, and total creatine (tCr) were determined.
Compared with the control group, mean NAWM mIns concentrations were significantly elevated in the MS group (4.56 mmol/L versus 3.75 mmol/L, P = .02) but not in the CIS group (4.04 mmol/L, P = .44). The higher concentration of mIns in the MS group was also reflected in the increased Ins/tCr ratio (P = .02). The mean NAWM tNAA was significantly decreased in both patient groups compared with the control group (CIS, 13.42 mmol/L, P = .02; MS, 12.77 mmol/L versus 14.51 mmol/L, P = .008).
A significant increase of the activity of the glial cells can only be observed in patients with an established diagnosis of MS but not in patients with CIS. Axonal damage occurs already during the first demyelinating episode in patients with CIS as well as in patients with definite MS.
American Journal of Neuroradiology 10/2007; 28(8):1517-22. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Infection of an intrathecal pump system is a rare but serious complication and usually leads to the removal of the pump. The authors report the first case of methicillin-resistant Staphylococcus aureus (MRSA) meningitis in a patient with such a pump successfully treated with linezolid without the need for removal of the intrathecal pump. A 77-year-old woman with cervical myelopathy underwent implantation of an intrathecal pump system for baclofen administration. Two weeks after the procedure she developed meningitis caused by MRSA as isolated in cerebrospinal fluid (CSF) cultures, blood samples, and serum obtained from the pump pouch. Clinically she presented with meningism, somnolence, and signs of sepsis. When a combined intravenous antibiotic treatment regimen of vancomycin and rifampicin resulted in no clinical improvement, that regimen was discontinued and linezolid was administered intravenously as monotherapy. Within 3 days clinical and laboratory findings showed significant improvement. After 1 week of linezolid treatment, blood and CSF cultures were sterile. Intravenous treatment was administered for a total of 3 weeks, after which the patient was treated with oral linezolid for 3 months. During 18 months of follow-up, no new clinical or laboratory signs of infection were observed. These results confirm previous reports of the efficacy of linezolid for the treatment of severe infections of the central nervous system caused by multidrug-resistant Gram-positive bacteria, especially postneurosurgical infections.
Journal of Neurosurgery 10/2007; 107(3):651-3. · 3.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: This paper aims to demonstrate the capabilities of a speed optimized T(2) weighted single-shot turbo spin echo sequence, using parallel imaging, variable flip angle refocusing and half-Fourier acquisition (FAS-TSE), in comparison with a standard TSE (sTSE) sequence in patients with suspected multiple sclerosis (MS). 33 patients presenting with a clinically isolated syndrome (CIS) suggestive of MS were prospectively examined on a 3.0 T MR system using FAS-TSE and a sTSE sequence. The FAS-TSE (scan time 11 s) and the sTSE (scan time 122 s) were compared regarding lesion detectability, lesion contrast, grey/white matter contrast, overall image quality and artefacts. Scanning parameters affecting image contrast and spatial resolution were kept identical. 208 lesions were detected using the sTSE sequence compared with 183 lesions (88%) using the FAS-TSE. The FAS-TSE was rated inferior regarding lesion contrast. The mean value/range/standard deviation of the lesion/white matter contrast were 0.26/0.06-0.49/0.089, respectively, with the sTSE vs 0.21/0.04-0.40/0.081 with the FAS-TSE. The FAS-TSE was rated inferior regarding overall image quality, but superior regarding motion artefacts. The grey/white matter contrast was qualitatively judged as comparable for both sequences. FAS-TSE provides sufficient T2-SE contrast and diagnostic image quality for whole brain studies in 11 s. It is suited to reduce motion artefacts in restless patients and for fast acquisition of additional scanning planes.
The British journal of radiology 09/2007; 80(956):668-73. · 2.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hashimoto's encephalopathy is a rare complication of autoimmune thyroiditis not associated with thyroidal function decline. We report a 50-year-old man presenting with lower motor neuron symptoms evolving over 3 years and changes in behavior associated with attentive and cognitive impairment occurring in the last few months. Memory deficits, emotional instability, marked dysarthria, mild symmetric weakness of the lower extremities and fasciculations were the most striking clinical features. EEG was diffusely slow, cranial MRI revealed multiple subcortical white matter lesions, CSF protein was slightly elevated, electromyographic recordings showed acute and chronic denervation and extremely high TPO antibody titers were found in the serum. Hashimoto's encephalopathy and lower motor neuron disease were diagnosed. As repeated high-dose intravenous methylprednisolone administration followed by oral tapering improved both central nervous system and lower motor neuron symptoms, the question was raised whether there was a common autoimmune pathogenesis of both clinically distinct diseases.
Neurology India 10/2006; 54(3):301-3. · 1.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Current MR imaging criteria for multiple sclerosis (MS) do not specify the magnetic field strength. The aim of this study was to investigate whether different MR imaging field strengths, specifically high-field MR imaging, have an impact on the classification of patients with clinically isolated syndromes suggestive of MS, according to MR imaging and diagnostic criteria.
In a prospective intraindividual comparative study, we examined 40 patients with clinically isolated syndromes (CIS) consecutively with a 1.5 T and 3T MR imaging system, including axial sections of T2 turbo spin-echo, fluid-attenuated inversion recovery, and T1 spin-echo, before and after injection of gadolinium-diethylene-triaminepentaacetic acid. Constant resolution parameters were used for both field strengths. High-signal-intensity white matter lesions with a size of >3 mm were counted and categorized according to their anatomic location in infratentorial, callosal, juxtacortical, periventricular, and other white matter areas. Assessment of the fulfilled Barkhof MR imaging and McDonald diagnostic criteria was made separately for both field strengths in every patient.
Eleven patients fulfilled more MR imaging criteria at 3T. Two of these patients fulfilled the criterion of dissemination in space (DIS) according to the first definition of McDonald criteria, which is based on imaging criteria alone. Another patient had DIS only at 3T, according to the second definition of the McDonald criteria including CSF parameters.
MR field strength, specifically high-field MR imaging, has a substantial influence on the classification of patients with CIS according to imaging and a mild influence on the classification according diagnostic criteria for MS, leading to consequences for prognostic classification, imaging guidelines, and clinical trials.
American Journal of Neuroradiology 10/2006; 27(8):1794-8. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to determine the sensitivities in the detection of inflammatory lesions in patients with clinically isolated syndromes suggestive of multiple sclerosis at 3.0 T and 1.5 T. MR imaging of 40 patients at both field strengths was performed in separate sessions including contiguous axial slices of T2 turbo spin-echo (T2 TSE), fluid-attenuated-inversion-recovery (FLAIR) and pre- and postcontrast T1 spin-echo (T1 SE). Inflammatory lesions > 3 mm in size were counted and categorized according to their anatomic location. Lesion conspicuity was assessed on a five-point scale. At 3.0 T, 13% more white matter lesions could be identified on the FLAIR sequence and on the T2 TSE sequence. Compared to 1.5 T 7.5% more contrast-enhancing lesions were detected at 3.0 T. The higher detection rate at 3.0 T was significant for the infratentorial (p = 0.02) and juxtacortical (p < 0.01) region on the FLAIR as well as for the infratentorial (p = 0.03), juxtacortical (p = 0.02) and periventricular (p = 0.03) region on the T2 TSE sequence. The lesion conspicuity was significantly better at 3.0 T for FLAIR and T2 TSE sequences (p<0.01; p=0.01). In conclusion, high-field MRI at 3.0 T provides a significantly higher detection rate of inflammatory brain lesions especially in the infratentorial, juxtacortical and periventricular anatomic region.
European Radiology 10/2006; 16(9):2067-73. · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aims of this study were to determine and compare the sensitivity of T2 turbo spin-echo (T2 TSE) and fluid-attenuated inversion recovery (FLAIR) sequences at 3.0 T in the detection of inflammatory lesions in patients with clinically isolated syndromes suggestive of multiple sclerosis. Forty-nine patients were examined with a 3.0 T MRI system using 5 mm axial sections of T2 TSE (2:19 min), FLAIR (4:00 min) and pre- and postcontrast T1 spin-echo sequences (3:37 min). Brain lesions were counted and categorized according to their anatomic location. Patients were classified according to Barkhof MRI criteria for FLAIR and T2 TSE sequences. The FLAIR sequence detected more lesions in every anatomic region except for the infratentorial region. The higher sensitivity was significant for the total number of lesions (p<0.01), the juxtacortical (p<0.01), and the periventricular (p=0.01) region. A 9% increase of infratentorial lesions using the T2 TSE sequence was not significant. The higher sensitivity using the FLAIR sequence resulted in one additional MRI criterion in nine patients, whereas the better detection of infratentorial lesions using the T2 TSE sequence resulted in additional MRI criteria in three patients. In conclusion, FLAIR provides the highest sensitivity when compared with the T2 TSE, although T2 TSE still has a diagnostic relevance in terms of MRI criteria classification.
European Radiology 07/2006; 16(7):1494-500. · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: In multiple sclerosis (MS), a crucial step in the induction phase of the inflammatory process in the central nervous system (CNS) is the disruption of the endothelial blood-brain barrier (BBB). Its permeability depends on the expression of intercellular adhesion molecules, such as vinculin and N-cadherin in endothelial cells. Interferon-gamma (IFN-gamma), as a proinflammatory cytokine, decreases the expression of both adhesion molecules in epithelial and astrocytic cells, whereas IFN-beta1a, an established treatment for MS, increases the expression of N-cadherin and vinculin in astrocytic cells and is postulated to preserve endothelial cell barrier function and to inhibit transendothelial migration of activated leukocytes. We analyzed the expression of N-cadherin and vinculin in a murine brain endothelial cell line by immunofluorescence staining and Western blot to study the presumed reversal effects of IFN-beta1a (Rebif, Serono Pharma, Unterschleissheim, Germany) and IFN-gamma on the formation of intercellular contacts. Vinculin and N-cadherin expression in brain endothelial cells was decreased after treatment with IFN-gamma, whereas stimulation with IFN-beta1a caused increased expression of both adhesion molecules. Combined treatment with both IFNs did not affect vinculin and N-cadherin expression. These data suggest that IFN-gamma contributes to BBB disruption by decreasing and IFN-beta1a restores the BBB by an upregulation of vinculin and N-cadherin expression in brain endothelial cells. This action of IFN-beta1a may contribute to its beneficial effects in MS therapy.
Journal of Interferon & Cytokine Research 01/2005; 24(12):711-6. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Acute transverse myelitis (ATM) is a pathogenetically heterogeneous inflammatory disorder of the spinal cord. Therefore, the identification of clinical and paraclinical features providing clues of the underlying etiologies is needed. The clinical presentation, blood and cerebrospinal fluid (CSF) findings as well as magnetic resonance imaging (MRI) and neurophysiological features were retrospectively analyzed in 45 unselected consecutive patients with ATM. Parainfectious ATM was diagnosed in 38% of patients. The underlying infectious agent, however, was identified only in a minority of patients. In 36% of patients, the etiology remained uncertain ("idiopathic" ATM) and in 22% ATM was the first manifestation of possible multiple sclerosis (ATM-MS) according to recently published diagnostic criteria. Spinal cord MRI showed signal alterations in 96% of the patients. In ATM-MS, monosegmental involvement of the spinal cord was most frequent while spinal cord involvement of two or more segments was more common in ATM of other etiologies. Of particular note, neurophysiological examinations showed evidence of peripheral nervous system (PNS) involvement in 27% of patients with ATM but not in patients with ATM-MS. Therefore, neurophysiological evidence of PNS involvement may provide additional discriminatory features between ATM-MS and ATM of other etiologies.
Journal of the Neurological Sciences 03/2004; 217(2):217-23. · 2.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Interleukin-6 (IL-6) plays an important role in the regulation of the inflammatory response in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Previous reports indicated that the C allele of a variable number tandem repeat (vntr) polymorphism located in the 3'flanking region of the IL-6 gene ( IL-6) is associated with reduced activity of IL-6 in vivo. Since disease-modifying genes are likely to contribute to phenotypic differences in MS patients, we tested the hypothesis that the IL-6 C allele is associated with the clinical course of MS. The IL-6 C allele was equally distributed between 217 MS patients of German Caucasian origin and 111 age-mached healthy controls. Stratification of patients according to the course of disease revealed no significant difference of IL-6 C allele distribution between patients with primary progressive and those with either relapsing-remitting or secondary progressive MS although IL-6 C allele was more frequent in patients with RR-MS. Since IL-6 C allele has been associated with a benign course in Sardinian MS patients, we further analysed an independent sample of 125 Sardinian MS patients revealing that IL-6 C allele was much more frequent than in German MS patients. Taken together, a disease-modifying effect of IL-6 C allele could not be demonstrated in MS patients of German Caucasian descent.
Journal of Neurology 06/2003; 250(5):607-11. · 3.58 Impact Factor